Keith G. Kramlinger

The Stanley Foundation Bipolar Treatment Outcome Network. I. Longitudinal methodology.

The NIMH-Stanley Foundation Bipolar Treatment Outcome Network, a multisite clinical trials network, has been established to address many of the neglected areas of research in bipolar illness. The Network was designed so that it would be able to conduct randomized clinical trials at several different levels of methodologic rigor (blinded and open-label) both in academic and community practice settings in order to better assess long-term efficacy of existing treatments and develop new ones. In this fashion, large numbers of representative patients with bipolar disorder have been enrolled with an additional focus of elucidating possible clinical and biological predictors of treatment response. The unique focus of the Network is its systematic longitudinal approach to illness so that patients can be assessed comprehensively over the long-term in sequential randomized clinical trials at critical clinical decision points where data on relative efficacy are inadequate. Bipolar I and bipolar II patients with a range of illness variants and comorbidities are included. Daily prospective ratings of severity of mania and depression and associated degree of functional impairment are completed on the NIMH-Life Chart Method and a modified Clinical Global Impressions Scale for Bipolar Illness (CGI-BP) is utilized. More detailed cross-sectional ratings for depression (Inventory of Depressive Symptomatology), mania (Young Mania Rating Scale), and psychosis (Positive and Negative Syndrome Scale) are additionally used at academic centers. This article describes the rationale for the Network, its guiding principles, methods, and study design to systematically assess the highly variable course of bipolar illness and its response to current and future treatments.

Rapid cycling bipolar affective disorder: Lack of relation to hypothyroidism

Thyroid indices were measured after an extended period of medication-free evaluation averaging 6 weeks in 67 consecutively admitted patients with bipolar illness. Thyroid hormone levels -- thyroxine (T4), free T4 and triiodothyronine (T3) -- were not significantly different in the 31 rapid cyclers (> or = 4 affective episodes/year) than in 36 non-rapid cyclers. Analysis of covariance indicated a non-significant trend relation between higher T4 and a greater number of affective episodes in the year prior to admission and male gender when age was covaried. Several previous reports, primarily in medicated subjects, have suggested a link between rapid cycling patients and decreased peripheral thyroid indices (low hormone levels and elevated TSH), but now the majority of studies do not support such a relation. Among those in the literature, this study includes patients studied for the longest time off medications and further suggests that the commonly-cited relation between subclinical hypothyroidism and rapid cycling bipolar illness be reevaluated.

Rash Complicating Carbamazepine Treatment

Carbamazepine–widely used in the treatment of trigeminal neuralgia, seizure disorders, and more recently, manic-depressive illness–is generally safe and well tolerated. Although serious adverse reactions, such as hematologic toxicity, may occur rarely, we have found that carbamazepine-induced rash is common, occurring in 13 (12%) of 113 patients. We describe our experience with carbamazepine-induced rash, including clinical characteristics, demographic features, and associated laboratory findings. Integrating our findings with the literature, we also discuss incidence, possible mechanisms, and implications for treatment because these benign rashes can occasionally progress to more fulminant and life-threatening eruptions.

Effect of cyclical unipolar depression on upper gastrointestinal motility and sleep

Cyclic 48-h unipolar depression is a rare form of recurrent affective disorder. We studied a single patient to determine (a) if there is an association between psychiatric status and migrating motor complex activity; and (b) if phase III of the migrating motor complex is in phase with rapid eye movement sleep in depression. There was marked reduction in phase III of the migrating motor complex during the depressed (n = 7) compared with the euthymic phase (n = 13), and a lack of coherence between phase III migrating motor complex activity and sleep stages in both depressed and nondepressed phases. The depressed state may be associated with altered upper gastrointestinal motor function.